Danish Prostate Cancer Consortium Study 1 (DPCC-1) protocol: Multicentre prospective validation of the urine-based three-microRNA biomarker model uCaP

Introduction
The primary objective of the Danish Prostate Cancer Consortium Study 1 (DPCC-1) is to provide validation for a novel urine-based microRNA biomarker, called uCaP, for a diagnosis of prostate cancer.

Methods and analysis
Eligible participants are biopsy naïve men aged ≥18 years with prostate-specific antigen (PSA) levels ≥3 ng/mL, who are referred to prostate MRI due to suspicion of PC at one of the following three major urology/uroradiology centers: Aarhus University Hospital, Herlev & Gentofte University Hospital, or Odense University Hospital, where MRI and targeted biopsy are implemented in clinical use. Exclusion criteria include previous diagnosis of urogenital cancer, contraindication to MRI, gender reassignment treatment or PSA level >20 ng/mL. The participants will be asked to donate a urine sample in connection with their MRI. The study is observational, uses a diagnostic accuracy testing setup and will integrate into the current diagnostic pathway.
We will measure the levels of the three microRNAs in the uCaP model (miR-222–3 p, miR-24–3 p and miR-30c-5p) in extracellular vesicle-enriched cell-free urine samples, to assess if uCaP can improve specificity and retain sensitivity for International Society of Urological Pathology Grade Group ≥2 PC, when used as a reflex test to PSA ≥3 ng/mL. We hypothesise that uCaP can improve selection for prostate MRI and reduce the number of unnecessary scans and biopsies.

Ethics and dissemination
This study is approved by the Central Denmark Region Committee on Health Research Ethics (reference number: 1-10-72-85-22). All participants will provide written informed consent. Study results will be published in peer-reviewed journals and presented in scientific meetings.

Trial registration number
NCT05767307 at clinicaltrials.gov.

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Novembre 2023

Abstract 13867: Sustained Improvement in Door-to-Balloon Time Over 15 Years: The Aurora St. Luke’s 24×7 STEMI Program With Redefinition of Contemporary Door-to-Balloon Time Less Than 60 Minutes: 60 is the New 90

Circulation, Volume 148, Issue Suppl_1, Page A13867-A13867, November 6, 2023. Background:In April 2004, Aurora St. Luke’s Medical Center implemented an in-house 24×7 interventional cardiology program to improve door-to-balloon time (D2BT) in ST-segment elevation myocardial infarction (STEMI). Previously published data showed a significant reduction in median D2BT, from 98 minutes (January 1, 2002-March 31, 2004) to 55 minutes (April 1, 2004-June 30, 2008), along with a reduction in major adverse cardiovascular events (MACE) and mortality after implementation of the program.Hypothesis:We hypothesized that the continued experience with the 24×7 program would demonstrate further gain in STEMI outcomes in regard to D2BT.Aims:The primary objective was to evaluate the overall median D2BT over a 15-year period. The secondary objectives were to evaluate median D2BT stratified by weekdays and weekends, on- and off-hours, the proportion of D2BT

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Novembre 2023

Abstract 18219: J-Shaped Association Between LDL-Cholesterol Level and Cardiovascular Events: A Longitudinal Follow-Up Study Over 2.4 Million Nationwide Primary Prevention Cohort

Circulation, Volume 148, Issue Suppl_1, Page A18219-A18219, November 6, 2023. Introduction:Low-density lipoprotein (LDL)-cholesterol lowering treatment showed benefits in patients with high atherosclerotic cardiovascular disease (ASCVD) risk.Hypothesis:Although high LDL-cholesterol level is known to increase ASCVD risks, prognostic implications of low LDL-cholesterol level remain elusive.Methods:Using the data from a Korean Nationwide Cohort, we included 2,432,471 subjects without previous ASCVD. From 2009, subjects were followed for myocardial infarction (MI) and ischemic stroke until 2018. Subjects were stratified according to 10-year ASCVD risks (

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Novembre 2023

Abstract 18004: Impact of a Urine Sodium Guided Treatment Protocol on Acute Heart Failure Length of Stay: A Single Center Quality Improvement Study

Circulation, Volume 148, Issue Suppl_1, Page A18004-A18004, November 6, 2023. Introduction:Inpatient management of acute decompensated heart failure (ADHF) is associated with high costs and in-hospital complications. Traditional methods of assessing response to loop diuretics for ADHF is prone to inaccuracies that may contribute to costs and complications. More objective evidence-based methods of treating ADHF are needed to improve outcomes for these patients.Hypothesis:We hypothesize a treatment algorithm using Una as an objective marker of response to loop diuretics can decrease hospital length of stay (LOS) for patients with ADHF.Methods:This quality improvement study took place at a single urban academic center. 3 plan do study act (PDSA) cycles were performed to study the impact of the intervention on key quality metrics. The first two PDSA cycles took place on two medical teams over the course of two weeks each. The third PDSA cycle took place on all medical teams over the course of 5 months. Median hospital LOS, rates of readmission and acute kidney injury (AKI), and protocol use rates were calculated.Results:An average of 78 patients per month were admitted with ADHF. Protocol implementation rate was 58%. Patients in the first two PDSA cycles with ADHF who were managed with the UNa protocol on average had lower hospital LOS by 1 day and similar rates of acute kidney injury (AKI). Patients in the third PDSA cycle, however, did not experience any change in hospital LOS or AKI. Readmission rates were stable across all PDSA cycles.Conclusions:Protocoling the implementation of spot uNa to diuretic management in a large academic hospital required extensive multi-disciplinary coordination. While there was no observable impact on key quality metrics, maintaining high levels of protocol adherence remains a challenge. The impact of acute and chronic kidney injury on Una-protocol performance should be evaluated. Finally, the efficacy of a Una-based treatment approach across diverse patient demographics must be better understood.

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Novembre 2023

Abstract 13951: Change in Albuminuria Measured by Urine Albumin-to-Creatinine Ratio (UACR) and Associated Clinical Outcomes in Patients With Chronic Kidney Disease (CKD) Associated With Type 2 Diabetes (T2D)

Circulation, Volume 148, Issue Suppl_1, Page A13951-A13951, November 6, 2023. Introduction:The impact of change in albuminuria measured by UACR on key clinical outcomes (overall survival [OS], a composite cardiovascular [CV] outcome, and kidney disease progression) in patients (pts) with CKD associated with T2D is understudied.Hypothesis:A decreased UACR is associated with a lower risk of clinical outcomes, while an increased UACR is associated with a higher risk of clinical outcomes.Methods:Adult pts with an elevated UACR ≥30 mg/g (initial test) after T2D and CKD diagnosis were identified from the Optum EHR database (1/2007-9/2021). UACR change was categorized as increased ( >30% change), stable (-30% to 30%), or decreased (30% UACR decrease was associated with a lower long-term risk of overall mortality, CV events, and kidney disease progression. These findings highlight the importance of albuminuria monitoring in these pts.

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Novembre 2023

Abstract 17326: Urine Exosomes Proteomics for Parenchymal Kidney Health in Heart Failure Patients With Mechanical Circulatory Support

Circulation, Volume 148, Issue Suppl_1, Page A17326-A17326, November 6, 2023. Introduction:Kidney dysfunction frequently affects heart failure (HF) patients with left ventricular assist device (LVAD) support and is linked to unfavorable outcomes. However, the effects of LVAD support on parenchymal kidney health are uncertain. We performed a pilot study on urine exosome proteomics in LVAD recipients as they offer a non-invasive glimpse into kidney cellular states.Methods:We collected urine samples from 33 patients who underwent LVAD (HeartMate III) surgery between 01/2022-02/2023. Urine exosomes were isolated from the samples collected before the operation and on the 7th day after surgery. The exosome fraction underwent untargeted proteomics using LC-MS/MS and iBAQ quantification. Our investigation focused on identifying and studying kidney-enhanced proteins.Results:The exosomes isolated were verified by canonical exosome proteins (CD63, Hsp70) and TEM imaging (Fig.A,B), with 82.7% of exosomes between 51-120 nm (Fig.C). Over 7K strict genes were identified with an average of 1,150 proteins (Fig.D,E). In GO analysis, exosomes were the primary cellular compartment represented (Fig.F). A total of 176 kidney-enhanced proteins were present in >50% of samples. Differential expression analysis revealed 8 proteins with increased expression on the 7thday after surgery with FDR

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Novembre 2023

Abstract 110: Brain Injury Biomarkers Are Associated With Poor Neurological Outcomes Within 24 Hours After Refractory VT/VF Cardiac Arrest Requiring Extracorporeal Cardiopulmonary Resuscitation

Circulation, Volume 148, Issue Suppl_1, Page A110-A110, November 6, 2023. Background:Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging method that improve survival after refractory VF/VT cardiac arrest. Neuron-specific enolase (NSE) and S-100B are used to predict neurological outcome; however, it is unclear the reliability and earliest time point during ECPR.Methods:Single-center, retrospective cohort study included OHCA patients who underwent ECPR at the University of Minnesota between December 2015 and January 2023. NSE and S100B levels were obtained at admission, at 12 and 24h after ROSC in a total of 361 unconscious patients. The primary outcome was poor neurological outcome (defined as CPC 3-5) at hospital discharge. We evaluated the optimal cut-off levels for NSE and S100B by maximizing the Youden index and ROC analyses for poor clinical results. Finally, NSE and S100B at 12h and 24h were added to a multivariable logistic model (age, sex, bystander and witnessed).Results:Of 361 patients, 170 survived to hospital admission. Of these 85% (145/170) survived neurologically favorable. Mean (SD) NSE (ng/mL) values were significantly higher in the CPC 3-5 group at every time point, 52.3 (53) vs 21.1 (12) on admission; 92.8 (92) vs 20 (10) after 12h; 107.1(94.4) vs 21.5 (12.9) after 24h; p

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Novembre 2023

Abstract 16852: Pathological ECG Findings in 24-h-Holter-ECGs in Patients With Ischemic Stroke

Circulation, Volume 148, Issue Suppl_1, Page A16852-A16852, November 6, 2023. Introduction:ECG-monitoring covering several days is recommended by current guidelines to detect atrial fibrillation (AF) and other arrhythmias in stroke patients. In practice, the extent of rhythm monitoring varies. Here, we use data from the 24-hour screening-Holter-ECGs of the ongoing randomized multicenter trial Find-AF 2 to assess the rate of AF and other arrhythmias.Methods and Results:Find-AF 2 (NCT04371055) is a randomized and controlled open-label parallel multicenter trial with central AF adjudication (intervention arm) and blinded endpoint assessment. Patients ≥60 years with recent (≤30 days) ischemic strokes according to the AHA/ASA definition of any etiology are screened for eligibility. All eligible patients receive a 24-hour Holter-ECG prior to randomization. Holter ECG data are analyzed by the core laboratory using dedicated analysis software and following a predefined standard operation procedure. In this analysis, we included all 24-hour Holter-ECGs up to June 1, 2023.We analyzed 3742 24-hour-Holter-ECGs from 51 different centers and found new arrhythmias in 120 patients (3.2%). AF was detected in 61 patients (1.6%) with a median duration of the longest episode of 730 minutes [interquartile range (IQR) 220;1180] (see Figure 1). This led to the initiation of anticoagulation in all 61 patients (100%). In 47 patients (1.3%), pauses >2.5 s (mean 3.1s±0.5s; longest pause 4.8s) or relevant bradycardias

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Novembre 2023

Abstract 209: The Relationship Between the Ratio of Urine Osmolality to Serum Osmolality and Neurological Outcome of Out-of-Hospital Cardiac Arrest Patients

Circulation, Volume 148, Issue Suppl_1, Page A209-A209, November 6, 2023. Background:Progressive hypoxic brain injury after cardiac arrest can affect serum osmolality (SOsm) and urine osmolality (UOsm) in out-of-hospital cardiac arrest (OHCA) patients. This study aimed to examine the association between the ratios of UOsm to SOsm (USRs) within 3 days after return of spontaneous circulation (ROSC) and neurological outcomes in OHCA patients.Methods:The present study was prospective observational study and included OHCA patients with targeted temperature management (TTM) at Chonnam National University Hospital in Gwangju, Korea, between January 2016 and December 2022. We collected SOsm and UOsm at admission and at 24 h, 48 h, and 72 h after ROSC. We assessed the predictive performance of USRs to determine neurological outcome at discharge.Results:A total of 319 patients were included. UOsm levels and USRs at admission and 24 h, 48 h, and 72 h after ROSC in patients with poor outcome were lower than those in patients with good outcome. In multivariable analysis, the USRs at 24 h (odd ratio [OR], 0.363; 95% confidence interval [CI], 0.221-0.594), 48 h (OR, 0.451; 95% CI, 0.268-0.761), and 72 h (OR, 0.559; 95% CI, 0.357-0.875) after ROSC were independently associated with poor neurological outcome at discharge. The area under the receiver operating characteristic curves of USRs at admission and 24 h, 48 h, and 72 h after ROSC for predicting neurological outcome at discharge were 0.615 (95% CI, 0.559-0.669), 0.711 (95% CI, 0.658-0.760), 0.724 (95% CI, 0.671-0.772), and 0.751 (95% CI, 0.699-0.797).Conclusions:The USRs within 3 days of ROSC were associated with poor neurologic outcome at discharge in OHCA patients.

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Novembre 2023

Abstract 12182: Importance of Comorbidities in 24-month AF-Free Survival After Catheter Ablation

Circulation, Volume 148, Issue Suppl_1, Page A12182-A12182, November 6, 2023. Background:Presence of cardiac and non-cardiac comorbidities is reported to affect success of catheter ablation (CA) of atrial fibrillation (AF), however their predictive value in 1 and 2 year AF free survival is not reported.Research Questions:Which cardiac and non-cardiac comorbidities are most useful in predicting AF free survival after a single CA for paroxysmal and persistent AF.Goals:Create a model to identify potential risk factors that may reduce the long term success of catheter ablation for patients with AF to allow for risk modificationMethods:We included 1435 patients with symptomatic AF undergoing first time CA in 1 of 8 Hospitals of Northwell Health and follow ups for at least 24 months ablation. Baseline echocardiographic and laboratory data were extracted from our common EMR, and clinical outcomes were determined after manual review of the 6, 12 and 24 month visit. Baseline patient characteristics included age, gender, BMI, diagnoses, laboratory and echocardiographic measures used in a stepwise estimation logistic regression model using STATA /IC 16.1.Results:From our patient cohort (age 67.1±10.4, 565 female, 645 persistent), 28% of patients had AF recurrence within the 1st year, and 32.5% within 2 years. Multivariate analysis identified persistent AF as the only independent risk factor for AF recurrence within 12 months (P=.001). For 24-month recurrence the independent predictors were LVEF (p=.014), Diabetes Mellitus (p=.045), cardioversions prior to ablation (DCCV) (p=.001), and pulmonary disease (p=.001). Energy modality was not a significant predictor of AF recurrence. Hypertension (p=.008) was found to be negatively associated with AF recurrence. Our prediction model (Figure 1) for AF recurrence 24 months post-CA produced an ROC curve of 0.8048 and was 77% accurate.Conclusion:The presence of baseline comorbidities implies that such comorbidities, rather than procedural failure, are mostly related with AF recurrence after 1 year.

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Novembre 2023